Effects of portable non-invasive ventilation on exercise tolerance in patients with COPD

Breathlessness is the dominant symptom that limits exercise tolerance in patients with COPD. Several ergogenic approaches have been employed to improve exercise tolerance in this population including bronchodilators, oxygen and heliox supplementation, intermittent exercise and non-invasive ventilation (NIV). Although application of NIV during exercise is beneficial for increasing exercise capacity in patients with COPD, there are several disadvantages that limit its wider application during exercise, including lack of compliance with the equipment, and the time required to set up and supervise the equipment in the setting of pulmonary rehabilitation. Recent advances in technology have facilitated the development of portable non-invasive ventilation (pNIV) devices aiming to alleviate breathlessness during activities of daily living. The VitaBreath (Philips, Respironics) was developed in 2016 as a portable, handheld, battery powered, bi-level, NIV device, providing fixed positive inspiratory and expiratory airway pressure support (IPAP:18 and EPAP: 8 cmH2O, respectively). Accordingly, this dissertation aimed to investigate the physiological effects of pNIV application during controlled laboratory exercise conditions and activities of daily living, in patients with advanced COPD. As the VitaBreath device is no longer commercially available, but similar devices may come to market, the present dissertation provides proof of concept on how pNIV can be applied intermittently during exercise in patients with COPD, and how to select patients most likely to respond to pNIV. This in turn may encourage the development of more suitable devices. Intermittent exercise was chosen to evaluate the effects of pNIV in comparison to the commonly adopted pursed lip breathing (PLB) technique, as this type of exercise allowed regular application of the pNIV device or the PLB technique during recovery periods. Patients retained the device for 3 months to investigate the acceptability, comfort and usability of the device during activities of daily living. Twenty-four COPD patients were randomised to perform two intermittent exercise protocols sustained at different work intensities (60% WRpeak for 6-min and 80% WRpeak for 2-min) alternated with 2-min rest periods. Within each intermittent exercise modality, patients performed two identical exercise tests using either pNIV or the PLB technique in a balanced order sequence, during the recovery phases of intermittent exercise. The findings of this study showed that with both intermittent protocols average endurance time was greater when pNIV was applied compared to PLB. Improvements in exercise tolerance were due to lower degrees of dynamic hyperinflation (DH) and breathlessness with pNIV compared to PLB. An important finding of the aforementioned study was that a subgroup of patients (8/24) failed to show a clinical important improvement in DH with pNIV compared to PLB and did not improve exercise tolerance. Analysis identified that these 8 patients experienced greater resting lung hyperinflation, greater exercise-induced DH and breathlessness, secondary to the adoption of a tachypnoeic breathing pattern with pNIV compared to PLB. Interestingly, these patients also reported less benefit from using the device at home, in terms of anxiety around breathlessness and recovery time from breathlessness. Considering the variation of response reported in the present thesis it is important that clinicians assess the response to pNIV on an individual basis. As with any new method, it was important to appreciate the physiological consequences of the acute application of pNIV on thoracoabdominal volume regulation and respiratory muscle recruitment (assessed by optoelectronic plethysmography), and central hemodynamic responses. Compared to PLB, acute application of pNIV was associated, in the majority of patients, with increased end-inspiratory and end-expiratory rib cage volumes and greater rib cage muscle recruitment, as well as decreased end-expiratory abdominal volumes reflecting reduced expiratory abdominal recruitment. Measurement of cardiac output revealed no adverse circulatory responses with the application of positive airway pressures provided by pNIV during the recovery periods. However, the pattern of thoracoabdominal volume regulation and respiratory muscle kinematics confirmed the findings of the original studies, thereby identifying responders and non-responders to pNIV. Interestingly, responders to pNIV exhibited greater recruitment of the expiratory abdominal muscles compared to non-responders, thereby facilitating them to combat end-expiratory rib cage dynamic hyperinflation effectively. When patients used the VitaBreath device during their daily physical activities, the majority of patients felt less anxious about becoming breathless and felt that their breathlessness recovered faster when using the device at home for 3 months. Moreover, almost all patients used the device at least weekly and all patients rated the ease of VitaBreath use to be between good and excellent. Additionally, most patients felt that using the device had benefited them and that they would recommend the device to other patients. The main disadvantage of the device was reported to be the high cost and its portability. The pNIV method provided fixed IPAP and EPAP. This represents a very important disadvantage of this particular pNIV device, which clearly mitigated the beneficial impact it had on some patients. Future research into pNIV devices should examine how best to identify patients who benefit from a pNIV method in everyday life. On-going development of auto-adjusted ventilators would facilitate a larger fraction of COPD patients to be physically active and experience a better quality of life

Use of pedometers as a tool to promote daily physical activity levels in patients with COPD: a systematic review and meta-analysis

The aim of this study was to examine the use of pedometers as a tool to promote daily physical activity levels in patients with COPD.A systematic review meta-analysis of pedometer physical activity promotion in patients with COPD was conducted. Medline/PubMed, Cochrane Library, Web of Science and CINAHL were searched from inception to January 2019. The search strategy included the following keywords: physical activity promotion, pulmonary rehabilitation and daily physical activity. The eligibility criteria for selecting studies were randomised controlled trials reporting pedometer physical activity promotion in patients with COPD.Improvements in steps per day were found with pedometer physical activity promotion either standalone (n=12, mean 0.53 (95% CI 0.29textendash0.77); p=0.00001) or alongside pulmonary rehabilitation (n=7, 0.51 (0.13textendash0.88); p=0.006). A subgroup analysis reported significant differences in the promotion of physical activity based on baseline physical activity levels and the type of instrument used to assess levels of physical activity.Future trials should consider the way in which pedometers are used to promote physical activity to inform clinical practice in the setting of pulmonary rehabilitation.Pedometer based physical activity promotion as a standalone intervention or alongside pulmonary rehabilitation induces meaningful improvements in daily physical activity levels (steps per day) in patients with COPD. http://bit.ly/2LnxM2

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits. Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR. In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389–0.687, and IRR 0.635, 95% CI 0.473–0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100–0.358, and IRR 0.375, 95% CI 0.207–0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072–0.185). Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR

Acute thoracoabdominal and hemodynamic responses to tapered flow resistive loading in healthy adults

We investigated the acute physiological responses of tapered flow resistive loading (TFRL) at 30, 50 and 70% maximal inspiratory pressure (PImax) in 12 healthy adults to determine an optimal resistive load. Increased end-inspiratory rib cage and decreased end-expiratory abdominal volumes equally contributed to the expansion of thoracoabdominal tidal volume (captured by optoelectronic plethysmography). A significant decrease in end-expiratory thoracoabdominal volume was observed from 30 to 50% PImax, from 30 to 70% PImax, and from 50 to 70% PImax. Cardiac output (recorded by cardio-impedance) increased from rest by 30% across the three loading trials. Borg dyspnoea increased from 2.36 ± 0.20 at 30% PImax, to 3.45 ± 0.21 at 50% PImax, and 4.91 ± 0.25 at 70% PImax. End-tidal CO2 decreased from rest during 30, 50 and 70 %PImax (26.23 ± 0.59, 25.87 ± 1.02 and 24.30 ± 0.82 mmHg, respectively). Optimal intensity for TFRL is at 50% PImax to maximise global respiratory muscle and cardiovascular loading whilst minimising hyperventilation and breathlessness

Interval versus constant-load exercise training in adults with Cystic Fibrosis

Background: The efficacy of interval exercise (IE) compared to constant-load exercise (CLE) training remains unsettled in adults with Cystic Fibrosis (CF). Methods: Twenty-four adults with CF were randomised to 30-min IE (100% peak work capacity (WRpeak) for 30-s alternated with 40% WRpeak for 30-s; n = 12) or 30-min CLE (70% WRpeak; n = 12) training, 3 times weekly, for 12 weeks. Isometric quadriceps muscle strength was assessed using a strain gauge Myometer. Results: The magnitude of improvement in quadriceps muscle strength was greater (p = 0.037) in the IE (by 32 ± 13 Nm) compared to the CLE (by 23 ± 12 Nm) groups. Maximum inspiratory and expiratory mouth pressures were significantly improved only in the IE group (by 30 ± 10 cmH2O; p = 0.009 and 13 ± 4 cmH2O; p = 0.007, respectively). Arterial oxygen saturation during training was higher (p = 0.002) for IE (94 ± 1%) compared to CLE (91 ± 1%), whereas dyspnoea scores were lower (p = 0.001) for IE (3.8 ± 0.7) compared to CLE (5.9 ± 0.8) Conclusions: IE is superior to CLE in improving peripheral and respiratory muscle strength and preferable to CLE because it is associated with lower exercise-induced arterial oxygen desaturation and breathlessness

Effect of portable non-invasive ventilation on exercise tolerance in COPD: One size does not fit all

In a cross-over RCT, portable NIV (pNIV) reduced dynamic hyperinflation (DH) compared to pursed lip breathing (PLB) during recovery from intermittent exercise in COPD, but not consistently in all subjects. In this post-hoc analysis, DH response was defined as a reduction ≥4.5 % of predicted resting inspiratory capacity with pNIV compared to PLB. At exercise iso-time (where work completed was consistent between pNIV and PLB), 8/24 patients were DH non-responders (DH: 240 ± 40 mL, p = 0.001 greater using pNIV). 16/24 were DH responders (DH: 220 ± 50 mL, p = 0.001 lower using pNIV). Compared to DH responders, DH non-responders exhibited greater resting DH (RV/TLC: 65 ± 4% versus 56 ± 2%; p = 0.028) and did not improve exercise tolerance (pNIV: 30.9 ± 3.4 versus PLB: 29.9 ± 3.3 min; p = 0.603). DH responders increased exercise tolerance (pNIV: 34.9 ± 2.4 versus PLB: 27.1 ± 2.3 min; p = 0.001). Resting RV/TLC% was negatively associated with the magnitude of DH when using pNIV compared to PLB (r=-0.42; p = 0.043). Patients with profound DH were less likely to improve exercise tolerance with pNIV. Further studies using auto-adjusted ventilators are warranted

Effect of portable noninvasive ventilation on thoracoabdominal volumes in recovery from intermittent exercise in patients with COPD

We previously showed that use of portable noninvasive ventilation (pNIV) during recovery periods within intermittent exercise improved breathlessness and exercise tolerance in patients with COPD compared with pursed-lip breathing (PLB). However, in a minority of patients recovery from dynamic hyperinflation (DH) was better with PLB, based on inspiratory capacity. We further explored this using Optoelectronic Plethysmography to assess total and compartmental thoracoabdominal volumes. Fourteen patients with COPD (means ± SD) (FEV1: 55% ± 22% predicted) underwent, in a balanced order sequence, two intermittent exercise protocols on the cycle ergometer consisting of five repeated 2-min exercise bouts at 80% peak capacity, separated by 2-min recovery periods, with application of pNIV or PLB in the 5 min of recovery. Our findings identified seven patients showing recovery in DH with pNIV (DH responders) whereas seven showed similar or better recovery in DH with PLB. When pNIV was applied, DH responders compared with DH nonresponders exhibited greater tidal volume (by 0.8 ± 0.3 L, P = 0.015), inspiratory flow rate (by 0.6 ± 0.5 L/s, P = 0.049), prolonged expiratory time (by 0.6 ± 0.5 s, P = 0.006), and duty cycle (by 0.7 ± 0.6 s, P = 0.007). DH responders showed a reduction in end-expiratory thoracoabdominal DH (by 265 ± 633 mL) predominantly driven by reduction in the abdominal compartment (by 210 ± 494 mL); this effectively offset end-inspiratory rib-cage DH. Compared with DH nonresponders, DH responders had significantly greater body mass index (BMI) by 8.4 ± 3.2 kg/m2, P = 0.022 and tended toward less severe resting hyperinflation by 0.3 ± 0.3 L. Patients with COPD who mitigate end-expiratory rib-cage DH by expiratory abdominal muscle recruitment benefit from pNIV application. NEW & NOTEWORTHY Compared with the pursed-lip breathing technique, acute application of portable noninvasive ventilation during recovery from intermittent exercise improved end-expiratory thoracoabdominal dynamic hyperinflation (DH) in 50% of patients with COPD (DH responders). DH responders, compared with DH nonresponders, exhibited a reduction in end-expiratory thoracoabdominal DH predominantly driven by the abdominal compartment that effectively offset end-expiratory rib cage DH. The essential difference between DH responders and DH nonresponders was, therefore, in the behavior of the abdomen

Greater exercise tolerance in COPD during acute interval, compared to equivalent constant‐load, cycle exercise: physiological mechanisms

The relative importance of ventilatory, circulatory and peripheral muscle factors in determining tolerance to exercise in patients with COPD is not known. In twelve COPD patients (FEV1 :58 ± 17%pred.) we measured ventilation, cardiac output, dynamic hyperinflation, local muscle oxygenation, blood lactate and time to exhaustion during a) interval exercise (IE) consisting of 30 s at 100% peak work-rate alternated with 30 s at 50% and b) constant load exercise (CLE) at 75% WRpeak, designed to produce the same average work rate. Exercise time was substantially longer during IE than CLE (19.5 ± 4.8 versus 11.4 ± 2.1 min, p = 0.0001). Total work output was therefore greater during IE than CLE (81.3 ± 27.7 versus 48.9 ± 23.8 kJ, p = 0.0001). Dynamic hyperinflation (assessed by changes from baseline in inspiratory capacity-ΔIC) was less during IE than CLE at CLE exhaustion time (isotime, p = 0.009), but was similar at exhaustion (ΔICCLE : -0.38 ± 0.10 versus ΔICIE : -0.33 ± 0.12 l, p = 0.102). In contrast, at isotime, minute ventilation, cardiac output and systemic oxygen delivery did not differ between protocols (p>0.05). At exhaustion in both protocols, vastus lateralis and intercostal muscle oxygen saturation were higher in IE than CLE (p = 0.014 and p = 0.0002, respectively) and blood lactate concentrations were lower (4.9 ± 2.4 mmol/l versus 6.4 ± 2.2 mmol/l, p = 0.039). These results suggest that 1) exercise tolerance in COPD is limited by dynamic hyperinflation; and 2) cyclically lower (50%) effort intervals in IE help preserve muscle oxygenation and reduce metabolic acidosis compared to CLE at the same average work rate, but these factors do not appear to determine time to exhaustion

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis

BACKGROUND: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. METHODS: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. RESULTS: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s$^{-1}$) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s$^{-1}$) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s$^{-1}$) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. CONCLUSION: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for

Laboratory and free-living gait performance in adults with COPD and healthy controls

BACKGROUND Gait characteristics are important risk factors for falls, hospitalisations and mortality in older adults, but the impact of COPD on gait performance remains unclear. We aimed to identify differences in gait characteristics between adults with COPD and healthy age-matched controls during 1) laboratory tests that included complex movements and obstacles, 2) simulated daily-life activities (supervised) and 3) free-living daily-life activities (unsupervised). METHODS This case-control study used a multi-sensor wearable system (INDIP) to obtain seven gait characteristics for each walking bout performed by adults with mild-to-severe COPD (n=17; forced expiratory volume in 1 s 57±19% predicted) and controls (n=20) during laboratory tests, and during simulated and free-living daily-life activities. Gait characteristics were compared between adults with COPD and healthy controls for all walking bouts combined, and for shorter (≤30 s) and longer (>30 s) walking bouts separately. RESULTS Slower walking speed (-11 cm·s$^{-1}$, 95% CI: -20 to -3) and lower cadence (-6.6 steps·min$^{-1}$, 95% CI: -12.3 to -0.9) were recorded in adults with COPD compared to healthy controls during longer (>30 s) free-living walking bouts, but not during shorter (≤30 s) walking bouts in either laboratory or free-living settings. Double support duration and gait variability measures were generally comparable between the two groups. CONCLUSION Gait impairment of adults with mild-to-severe COPD mainly manifests during relatively long walking bouts (>30 s) in free-living conditions. Future research should determine the underlying mechanism(s) of this impairment to facilitate the development of interventions that can improve free-living gait performance in adults with COPD